Description: (From the Applicant?s Description) The scientific focus of the Molecular and Genetic Toxicology Research Core is aimed at understanding the molecular mechanisms used by prokaryotic and eukaryotic cells to maintain the integrity of DNA and the mechanisms of cellular signaling through transduction pathways. The fundamental objective of this Core is to serve as an intellectual resource to facilitate interactive research centered in several areas including: (1) mechanisms of DNA damage and repair; (2) fidelity of DNA synthesis; (3) biosynthesis of deoxyribonucleoside triphosphates and their relationship to mechanisms of mutagenesis; (4) protein DNA binding mechanisms, structure, and function; (5) protein damage and modification; and (6) protein-protein interactions involved in signal transduction, DNA replication, and DNA repair pathways. Investigative approaches used by Core members cover a wide spectrum of techniques including gene cloning, enzyme/protein purification, protein chemistry, enzyme kinetics (steady-state and stopped-flow), nucleic acid manipulation and modification (site-directed mutagenesis and damaged DNA substrates), biosensor analysis of macromolecular interactions, metabolite pool assays, computer modeling, and nuclear magnetic resonance. Research in this Core is allied with the Nucleic Acids and Proteins Facilities and Service Core that is coordinated by Dr. Schimerlik.